Moringin, an isothiocyanate modulates multiple cellular signalling molecules in breast cancer cells

Authors

Ankit Srivastava, Banaras Hindu University
Shruti Mishra, Banaras Hindu University
Avadhesh, Banaras Hindu University
Anusmita Shekher, Banaras Hindu University
Vipin Rai, Banaras Hindu University
Anupam Dhasmana, The University of Texas Rio Grande Valley
Jayanta Das, All India Institute of Medical Sciences
Daniele Perenzoni, Fondazione Edmund Mach (FEM)
Renato Iori, Fondazione Edmund Mach (FEM)
Subash C. Gupta, Banaras Hindu University

Document Type

Article

Publication Date

4-21-2024

Abstract

Highlights

• The cancer patients with changes in Prohibitin (PHB) exhibit significantly reduced ‘overall survival’ in comparison to the cases without alterations in PHB.

• Moringin (MG) is an isothiocyanate that can induce apoptosis in breast cancer cells.

• MG can trigger depolarization in mitochondrial membrane potential suggesting that MG induced apoptosis involves mitochondria.

• MG can suppress p65 nuclear translocation and can modulate lncRNAs expression in breast cancer cells.

• The activities of MG against breast cancer might result from its ability to modulate multiple cancer-related targets.

Abstract

Prohibitin (PHB) is a pleiotropic molecule with a variety of known functions and subcellular locations. PHB's function in breast cancer is poorly understood. Herein, we report that PHB is expressed in cancer types of diverse origin including breast cancer. The cancer patients with changes in PHB were reported to have significantly reduced ‘overall survival’ in comparison to the cases without alterations in PHB. The expression of PHB was increased by H2O2 and also by Moringin (MG), which is an isothiocyanate derived from the seeds of Moringa oleifera. MG interacted with PHB, DRP1, and SLP2 and inhibited the growth of MCF-7 and MDAMB-231 cells. The isothiocyanate triggered apoptosis in breast cancer cells as revealed by AO/PI assay, phosphatidylserine externalization, cell cycle analysis and DAPI staining. MG induced proapoptotic proteins expression such as cytochrome c, p53, and cleaved caspase-7. Further, cell survival proteins such as survivin, Bcl-2, and Bcl-xL were suppressed. A depolarization of membrane potential suggested that the apoptosis was triggered through mitochondria. The isothiocyanate suppressed the cancer cell migration and interacted with NF-κB subunits. MG suppressed p65 nuclear translocation induced by TNF-α. The reactive oxygen species generation was also induced by the isothiocyanate in breast cancer cells. MG also modulated the expression of lncRNAs. Collectively, the functions of PHB in breast cancer growth is evident from this study. The activities of MG against breast cancer might result from its ability to modulate multiple cancer-related targets.

Comments

Original published version available at https://doi.org/10.1016/j.cellsig.2024.111181

Recommended Citation

Srivastava, A., Mishra, S., Avadhesh, Shekher, A., Rai, V., Dhasmana, A., Das, J., Perenzoni, D., Iori, R., & Gupta, S. C. (2024). Moringin, an isothiocyanate modulates multiple cellular signalling molecules in breast cancer cells. Cellular signalling, 111181. Advance online publication. https://doi.org/10.1016/j.cellsig.2024.111181

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

Cellular Signalling

DOI

10.1016/j.cellsig.2024.111181

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology